Here, Press Association Sport looks at how the Argentinian has fared against the Red Devils during his time as a manager in England.
Pochettino has a mixed record against United in 13 games as Southampton and Tottenham boss, winning four, losing six and drawing three. He did not beat United at all while at Southampton, although there was only one defeat in three games with Saints – that coming in just his second game in charge in January 2013. Wayne Rooney scored twice as Sir Alex Ferguson's then Premier League leaders came from behind to win 2-1.
At Spurs, Pochettino has faced United 10 times, collecting a win earlier this season and in each of the previous three campaigns. That is offset by five defeats while there has also been one draw.
Never achieved a double
Sunday's game will give Pochettino a chance to achieve a first double over United, having triumphed 3-0 at Old Trafford in August. That success was an early statement of Tottenham's power this season while it also increased the pressure on United boss Jose Mourinho, whose eventual sacking in December led to speculation linking Pochettino with the job. United will go into the game with momentum after winning four in succession under caretaker boss Ole Gunnar Solskjaer but they remain 10 points behind third-placed Spurs.
Prior to this season's win at Old Trafford, all of Pochettino's previous successes against United had come at home, either White Hart Lane or Wembley. In fact, putting aside last season's FA Cup semi-final at a neutral Wembley, United have never won away against a Pochettino Spurs side. That bodes well for them this weekend, although Pochettino has suffered at least one defeat to United in all but one of his five full seasons in England. The exception was 2013-14, when Southampton and United drew 1-1 twice.
The August success at Old Trafford probably ranks as Pochettino's best against United, a result that was secured with three goals in the second half. Harry Kane got the first of them before Lucas Moura grabbed two. Pochettino enjoyed another impressive 3-0 victory over United in April 2016 as Spurs tried to chase Leicester down in the title race. Their goals came from Dele Alli, Toby Alderweireld and Erik Lamela in a six-minute blitz midway through the second half.
The boot was on the other foot in March 2015 as Spurs were roundly beaten 3-0 at Old Trafford. Marouane Fellaini, Michael Carrick and Rooney all scored in the opening 34 minutes as Pochettino's side were outclassed and United enjoyed one of their best wins under Louis Van Gaal.